Association between gut microbiota, bone metabolism, and fracture risk in postmenopausal Japanese women.

INTRODUCTION: We investigated the relationship between gut microbiota composition and osteoporosis/fracture risk in Japanese postmenopausal women using 16S rRNA gene sequencing, FRAX, bone mineral density, biochemical bone parameters, and a self-administered questionnaire. Variation in abundance of specific microbiota was found to be significantly associated with fracture risk and vitamin K levels. Gut microbiota data with respect to bone metabolism and fracture risk is limited. Vitamin K is produced by certain intestinal bacteria and has been reported to play a role in maintaining bone quality. PURPOSE: We investigated relationships among gut microbiota composition, bone metabolism, and fracture risk in postmenopausal Japanese women. METHODS: Bone mineral density (BMD) was evaluated in 38 postmenopausal women (mean age 62.9 years) using forearm dual-energy X-ray absorptiometry. We collected and analyzed serum bone turnover markers (vitamin K fraction and tartrate-resistant acid phosphatase 5b; TRACP-5b), gut microbiota profiling (16S rRNA gene sequencing), and self-administered questionnaire data, including fracture history and vitamin K intake. Vitamin K2, BMD, and TRACP-5b data were divided into high- and low-level groups using cutoff values of 0.06 ng/mL, 87.05%, and 420 mU/dL, respectively; the proportions of bacteria were analyzed. Fracture incidence and relative risk were investigated for each bacterium. RESULTS: The genus Bacteroides was predominant in the high vitamin K2 group (29.73% vs 21.58%, P = 0.022). Fracture incidence was significantly higher in the low Bacteroides group, with a 5.6-times higher risk ratio of fracture history. The family Rikenellaceae was more abundant in the low BMD group and more abundant in the high TRACP-5b group (2.15% vs 0.82%, P = 0.004; 2.38% vs 1.12%, P = 0.013, respectively). CONCLUSION: Bacteroides and Rikenellaceae may be involved in bone metabolism and fracture risk. Further investigations of the underlying microbiota-related pathways in bone metabolism may reveal treatment strategies, and facilitate the prevention of osteoporosis.

Uterine adenosarcoma with sarcomatous overgrowth: a case report with cytology of overgrown poorly differentiated sarcoma and immunohistochemical identification of epithelial microinvasion.

In this report, we describe a case of adenosarcoma of the uterine corpus with overgrown and poorly differentiated sarcoma. The patient was an 80-year-old Japanese woman with abnormal genital bleeding. The endocervical biopsy showed undifferentiated carcinoma, and a cytologic examination at that time revealed the presence of cell types ranging from dispersed spindle to round atypical cells, suggestive of mesenchymal origin. The resected uterus had a polypoid mass in the corpus of the uterus and a solid white mass with the appearance of frank malignancy in the endocervix. The phyllode pattern was evident in the polypoid lesion and a diagnosis of adenosarcoma with sarcomatous overgrowth was made. The epithelial component was atypical with occasional microinvasion, which mimicked rhabdomyoblasts, but was easily identified as microinvasion by positive staining for epithelial, but not myogenic, markers. This case stresses the importance of the cytologic smear in the identification of frank sarcoma in an adenosarcoma, and it furthermore highlights the usefulness of immunohistochemistry in the distinction of epithelial microinvasion from rhabdomyogenic differentiation.

Spin-triplet superconductivity in UNi(2)Al(3) revealed by the (27)Al Knight shift measurement.

We report (27)Al Knight shift ( (27)K) measurement on a single-crystal UNi(2)Al(3) that reveals a coexistence of superconductivity and a spin-density-wave (SDW) type of magnetic ordering ( T(SDW) = 4.5 K). The spin part of (27)K, (27)K(s), does not change down to 50 mK across the superconducting (SC) transition temperature T(c) approximately 0.9 K. In contrast with the isostructural compound UPd(2)Al(3) ( T(c) approximately 2 K), which was identified to be a spin-singlet d-wave superconductor, the behavior of (27)K strongly supports that UNi(2)Al(3) , like UPt(3) and Sr(2)RuO(4), belongs to a class of spin-triplet SC pairing state superconductors.

Characterization of hyperplastic foci observed in surgical specimens of hepatocellular carcinoma.

By reviewing previous surgical specimens of hepatocellular carcinoma, 17 cases with hyperplastic foci (HPF) characterized by discernible increase in nuclear densities, could be histologically selected. Nuclear densities of HPF and control hepatic parenchyma were assessed quantitatively by counting the nuclear number of hepatic cells, and proliferating cell nuclear antigen labeling index was measured. HPF occurred multifocally, confined within a lobular unit, smoothly merging into surrounding hepatic parenchyma. Nuclear densities of HPF were 1.71 times greater than those of control hepatic parenchyma. The hepatocytes of HPF also showed significantly higher proliferative activities than those of control parenchyma. In addition, noticeable structural distortions, such as focal trabecular thickening or microacinar formation of hepatocytes, were sometimes observed in HPF. However, these HPF seemed to be distinguished from minute de novo hepatocellular carcinoma (HCC) or intrahepatic HCC metastasis, because of paucity of distinctive atypical changes, and intimate correlation with neighboring hepatocytes. Several adjacent HPF were aggregated to form a much larger unit of a hyperplastic area with loss of fibrous septa of liver cirrhosis. It was suggested that grossly detectable large regenerative nodules are produced via fusion of several adjacent HPF.

A case report of insufficiency fracture of the Fossa acetabuli in a patient with rheumatoid arthritis.

Aside from vertebral compression fractures, the most common site of insufficiency fractures is the pelvis and lower extremities. In the pelvis, the fractures usually occur in the ilium, the pubis and the ischium, but rarely in the fossa acetabuli. We report a severe insufficiency fracture of the fossa acetabuli in a 78-year-old woman with rheumatoid arthritis (RA). She had associated insufficiency fractures of the rib, the thoracic spine and the sacrum. In our case, senile osteoporosis was present before the onset of the fracture was recognized on radiographs, and RA and corticosteroid therapy might have further aggravated the porosis, resulting in the destruction of the fossa acetabuli. Regarding treatment for the fracture, a cemented total hip replacement without bone graft was attempted for several reasons such as the patient's activities, postoperative rehabilitation and the bone mass of the acetabulum. The postoperative course was satisfactory during study period. However, further follow-up is needed to monitor carefully how the patient will be in the future.

Multiple fish vertebra deformity in child with systemic lupus erythematosus: a case report.

We report an 11-year-old female patient with multiple fish vertebra deformity, which occurred in the course of treatment with corticosteroids for systemic lupus erythematosus (SLE). She was treated for SLE with predonisolone (30 mg per day) from April 2, 1996, and presented at our outpatient clinic for an osteoporosis check-up on April 27. She was 132 cm tall with-1.7 standard deviation of the average height, and X-ray examination revealed no evidence of osteoporosis in the spine. Bone mineral density (BMD) was 74.7% of the average BMD. Subsequently, she grew to 136 cm in September. However she began to have low back pain (LBP) from November, and received alfacalcidol. LBP deteriorated after pulse therapy with methylpredonisolone. In June 1997, X-ray examination revealed multiple fish vertebra deformity with 58.3% of the average BMD. Moreover her height had decreased to 131cm. She underwent combination therapy with elcatonin and alfacalcidol. In September 1999, she had no LBP nor progression of fish vertebra deformity. However she had no growth in height. Corticoseroids and SLE have multiple effects on bone metabolism, making the treatment of porosis complicated and difficult.

Hepatoid adenocarcinoma: a new clinicopathological entity and the hypotheses on carcinogenesis.

Hepatoid adenocarcinoma is reviewed in its clinicopathological and oncogenetic aspects. This variant of adenocarcinoma has been found to be an alpha-fetoprotein (AFP) -producing carcinoma arising in extrahepatic organs, and it mimics hepatocellular carcinoma in terms of morphology and function. Vascular invasion, usually prominent, is often complicated by extensive liver metastases. A prompt and accurate diagnosis of hepatoid adenocarcinoma is important because the prognosis is very poor compared with that of common types of adenocarcinoma. The characteristic features of hepatoid adenocarcinoma are summarized on the basis of our own experiences and the literature. In addition, a possible molecular mechanism that under-lies the ectopic appearance of the hepatic phenotype is discussed.

Interstitial invasion of well-differentiated hepatocellular carcinoma and subsequent tumor growth.

Pathological processes of interstitial invasion of hepatocellular carcinoma (HCC) were investigated in 125 autopsy and seven surgical cases, where selection focused on those occurring in well-differentiated HCC. The invasive pattern of well-differentiated HCC was characterized by the formation of streaks of tumor cell cords running along connective tissue fibers, referred to as a streak pattern. These cell cords were unaccompanied by reticulin frameworks and type IV collagen, which are consistent components of HCC parenchyma. The typical streak pattern was observed only in HCC cases and could be useful in differential diagnosis. Following progressive accumulation or proliferation of the tumor cells within the interstitium, many capillaries appeared between the cell cords while collagen fibers tended to disappear. The tumor cell cords then showed branching and were accompanied by reticulin frameworks, type IV collagen and sinusoidal blood spaces. In the setting of interstitial invasion of well-differentiated HCC, it is suggested that interstitial tissue is converted into HCC parenchyma via the aforementioned steps.

Comparative morphometric studies of benign and malignant intraductal proliferative lesions of the breast by computerized image analysis.

Using computerized image analysis, we newly devised a method for automatic quantitative evaluation of nuclear arrangements in variable proliferative intraductal (cribriform) lesions of the breast, by calculating angles of longest nuclear diameter to a horizon (LNDA). Internuclear correlation in the cribriform lesions was thus examined, comparing 22 benign and 62 malignant cases. In the malignant lesions, nuclear arrangements tended to be multidirectional, probably because of vertical nuclear arrangements toward acinar lumens as reflected by the wide distribution of LNDAs. Conversely, in the benign lesions, groups of nuclei tended to arrange toward one certain direction, forming a complex streaming pattern with the distribution of LNDAs usually producing a distinctive peak. Other conventional nuclear features, such as nuclear area, nuclear perimeter, shortest nuclear diameter (SND), and leading variables were also quantitatively assessed for multivariate analysis. It was noted that nuclear arrangements could represent a favorable discriminator. Linear discriminant function could classify 66 of the total 84 cases (78.6%) as being consistent with the diagnosis of pathologists. We conclude that internuclear arrangement could be a useful discriminating variable in benign and malignant breast lesions for the further development of an automatic analytic system.